Migratory Polyarthritis as a Paraneoplastic Syndrome

Carcinomatous polyarthritis (CP) is a rare paraneoplastic disorder that has been associated with a variety of solid tumors. It presents in a similar manner to other polyarticular disorders and often precedes detection of the underlying malignancy, making recognition critical. CP responds to the treatment of the neoplastic process. We present a patient who initially presented with asymmetric inflammatory polyarthritis who was later diagnosed with bronchogenic carcinoma. Following the case report we present our learning objectives, which include the differential diagnosis of inflammatory polyarthritis, diagnostic approach to CP, and features that distinguish it from other more common causes of polyarthritis. We conclude with a brief discussion of the pathophysiology and management of CP.     

Paraneoplastic Opsoclonus-myoclonus Syndrome with Anti-Hu and Anti-SOX-1 Antibodies after Immune-checkpoint Inhibitor Treatment Combined with Chemotherapy in a Patient with Small-cell Lung Cancer

A 69-year-old man with advanced small-cell lung cancer achieved partial remission after 3 courses of immunochemotherapy that included atezolizumab. Ten days after the last treatment, he developed paraneoplastic opsoclonus-myoclonus syndrome and required mechanical ventilation. Serology testing detected anti-Hu and anti-SOX-1 antibodies. Despite steroid pulse therapy, various anticonvulsants, continuous intravenous sedation, and a fourth course of chemotherapy without atezolizumab, his condition failed to improve. Paraneoplastic opsoclonus-myoclonus syndrome with autoantibodies after immune-checkpoint inhibitor treatment has not been reported previously. Although a causal relationship between immune-checkpoint inhibitors and paraneoplastic syndromes has been suggested, the mechanism remains unknown.     

Autoimmune Pancreatitis with Gastric Cancer: Some IgG4-related Diseases May Be Paraneoplastic Syndrome

A 70-year-old man was referred to our department for the treatment of early gastric cancer. Contrast-enhanced computed tomography (CT) incidentally showed diffuse enlargement of the pancreas with a capsule-like rim, and blood tests showed elevated serum IgG4 levels, leading to a diagnosis of autoimmune pancreatitis (AIP). Endoscopic treatment for gastric cancer was performed, and pathological findings showed adenocarcinoma with abundant IgG4-positive plasma cell infiltration. Thereafter, the serum IgG4 levels normalized, and the findings of AIP disappeared on CT without steroid treatment. These findings suggest that the gastric cancer activated an IgG4-related immune response, resulting in the development of AIP.     

Paraneoplastic Cerebellar Degeneration and Lambert-Eaton Myasthenic Syndrome with SOX-1 Antibodies

A 69-year-old man was admitted to our hospital for progressive muscle weakness in both lower limbs and limb ataxia (day 0). Nerve conduction studies showed low compound muscle action potential amplitudes at rest and increased amplitudes after maximum voluntary contraction. Blood testing revealed SOX-1 antibodies. He was diagnosed with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome (PCD-LEMS). He died from aspiration pneumonia on day 9. Small-cell lung carcinoma (SCLC), which had not been obvious on computed tomography, was found during the autopsy. Patients with PCD-LEMS who test positive for SOX-1 antibodies should be carefully evaluated for SCLC.     

Palmar Fasciitis and Polyarthritis Syndrome Associated with Lung Adenocarcinoma

Palmar fasciitis and polyarthritis syndrome (PFPAS) is a rare paraneoplastic rheumatic disease with characteristic features. We herein report a 77-year-old man with lung adenocarcinoma and contralateral pulmonary metastasis receiving chemotherapy who presented with progressive symmetrical flexion contractures associated with palmar fascial thickening and arthritis of both hands and shoulders. He was diagnosed with PFPAS as paraneoplastic manifestations. Salazosulfapyridine was not effective, but 15 mg/day of oral prednisolone improved his symptoms. Physicians should consider PFPAS and rule out malignancy in patients with arthritis in the extremities and flexion contractures associated with palmar fascial thickening.     

Paraneoplastic Polymyositis Due to Renal Cell Carcinoma in a Patient with Autosomal Dominant Polycystic Kidney Disease

We herein report a 70-year-old man with malaise and muscle weakness that had developed within a month. The patient also had abdominal fullness due to polycystic kidney disease. Severe proximal skeletal muscle weakness and mild elevation of creatinine kinase to 301 IU/L were noted. A muscle biopsy of the right bicep showed polymyositis. Computed tomography showed a right renal mass, and an analysis after right nephrectomy identified clear cell carcinoma. The muscle weakness subsided one month after nephrectomy and intravenous immunoglobulin therapy. Therefore, we suspect that the development of polymyositis in this patient was closely related to renal cell carcinoma.     

Paraneoplastic Sensory Polyneuropathy Related to Anti-PD-L1-including Anticancer Treatment in a Patient with Lung Cancer

Paraneoplastic neurological syndromes (PNS), such as sensory polyneuropathy, are rare, and serum neuronal antibodies that are used for diagnosing this syndrome are occasionally positive. Similarly, neurological immune-related adverse events due to immune checkpoint inhibitors (ICIs) are also rare. However, their etiologies and the relationship between them remain unclear. We herein report a patient with suspected small cell lung cancer who showed sensory polyneuropathy after treatment with atezolizumab in combination with cytotoxic agents (carboplatin and etoposide) and was doubly positive for serum anti-Hu and anti-SOX-1 antibodies. Treatment with ICI and cytotoxic agents may sometimes lead to the development of PNS.     

CV2/CRMP5-antibody-related Paraneoplastic Neurologic Syndrome Associated with Gastrointestinal Stromal Tumor

Paraneoplastic neurological syndrome (PNS) is a heterogeneous group of neurological disorders caused by immune-mediated inflammatory mechanisms. We herein report a 77-year-old man with CV2/CRMP5-antibody-related PNS associated with a gastrointestinal stromal tumor (GIST). He was admitted for forgetfulness and delusional behavior. His neurological symptoms were subacute, and a whole-body examination revealed a gastric GIST. Serology showed CV2/collapsin response mediator protein (CRMP)-5 antibodies. Partial gastrectomy was performed for the GIST, and the neurological symptoms and serum CV2/CRMP5 antibodies disappeared. No relapse has occurred since the surgery. PNS should be considered in patients with subacute neurological disorders.     

Pancytopenia with hypercellular bone marrow—a possible paraneoplastic syndrome in carcinoma of the lung: A report of three cases

Three patients with idiopathic pancytopenia and hypercellular bone marrow who developed carcinoma of the lung within two years of diagnosis are reported. All three patients had macrocytic anemia associated with a megaloblastic marrow in the presence of normal serum vitamin B12 and folic acid levels. Neutropenia with monocytosis, elevated serum muramidase and LAP scores, and increased fetal hemoglobin levels were also found. In all cases Ham's tests were negative with a normal bone marrow karyotype. In all three patients, pancytopenia due to myelodysplasia, a probable preleukemic state, was diagnosed initially prior to the appearance of carcinoma of the lung. One of the patients showed improved leukocyte and platelet counts during chemotherapy, while the other two died before chemotherapy could be administered. In the light of the above findings we suggest that carcinoma of the lung may be the cause of a paraneoplastic syndrome with pancytopenia, particularly in patients with a hypercellular marrow with a normal karyotype.     

Paraneoplastic vasculitic neuropathy: immunohistochemical studies on a biopsied nerve and post-mortem examination

Abstract. We studied a patient with paraneoplastic vasculitic neuropathy (PVN) associated with a carcinoma of the common bile duct. Immunohistochemical analysis of the biopsied sural nerve showed that the cellular infiltrates in the vascular lesions were composed primarily of CD8-positive T lymphocytes and macrophages. Pathogenic significance of the T-cell-mediated immunological reaction was suggested. Post-mortem examination revealed the absence of systemic vasculitis, which may be a characteristic feature of PVN. The patient responded to immunosuppressive treatment. We discuss the efficacy and the risk of immunosuppressive therapy for PVN.     

Paraneoplastic polyarteritis nodosa with cerebral masses: case report and literature review

Polyarteritis nodosa (PAN) as a paraneoplastic vasculitis is rarely described, especially in association with squamous cell carcinoma (SCC). Furthermore, only 5% of all PAN patients have central nervous system (CNS) involvement, almost exclusively in the form of cerebral infarction or intracerebral haemorrhage. We report the first case of PAN with multiple immunosuppressant‐responsive, cerebral vasculitic lesions in association with metastatic SCC.     

国内24例副肿瘤性天疱疮临床资料分析

目的了解国内副肿瘤性天疱疮的临床特点。方法通过计算机检索,总结国内24例副肿瘤性天疱疮患者的临床表现、辅助检查及治疗。结果Castleman瘤是我国副肿瘤性天疱疮患者最常伴发的肿瘤,其次是淋巴瘤、慢性淋巴细胞白血病;临床上副肿瘤性天疱疮常误诊的疾病依次是扁平苔藓、多形红斑和大疱性皮肤病;闭塞性细支气管炎是副肿瘤性天疱疮患者的主要死亡原因。结论早期诊断、治疗肿瘤和预防闭塞性细支气管炎是治疗副肿瘤性天疱疮的关键。     

Constrictive bronchiolitis associated with paraneoplastic autoimmune multi-organ syndrome

Background and objective:   Constrictive bronchiolitis is a rare and potentially fatal manifestation of paraneoplastic autoimmune multi-organ syndrome (PAMS), also called paraneoplastic pemphigus. The current review aimed to assess the frequency and clinical features of constrictive bronchiolitis occurring in patients with PAMS.
Methods:   A computer-assisted search of medical records identified 17 patients with PAMS seen during the period 1994–2007. Medical records, radiological studies and biopsy results were reviewed.
Results:   There were 10 men and 7 women; the median age at diagnosis of PAMS was 60 years (range 33–72 years). Non-Hodgkin's lymphoma and chronic lymphocytic leukaemia were the underlying neoplasms in over two-thirds of these patients. Constrictive bronchiolitis was diagnosed in three patients who had respiratory symptoms, severe airflow obstruction on pulmonary function testing and evidence of air trapping on CT scanning with no other identifiable cause for these findings. In contrast to previous reports, two of the three patients with constrictive bronchiolitis presented with skin and respiratory manifestations in the absence of a known neoplasm. Seven patients with PAMS died (41%) after a median interval of 13 months (range 1–33 months) and the deaths included two of the constrictive bronchiolitis patients who continued to worsen despite immunosuppressive therapy.
Conclusions:   In a minority of patients with PAMS, constrictive bronchiolitis occurs and tends to cause progressive airflow obstruction that responds poorly to immunosuppressive therapy. Constrictive bronchiolitis in these patients may be manifest prior to the discovery of the underlying neoplasm and the diagnosis of PAMS.     

Unilateral Proptosis (Exophthalmos) Caused by Axillary-Subclavian Venous Thrombosis in a Patient with Upper Extremity Arteriovenous Dialysis Fistula

Arterialization of orbital veins is most often due to dural arteriovenous malformations of the cavernous sinus area. We report an unusual case of unilateral proptosis (exophthalmos) caused by arterialized retrograde venous flow in the external jugular vein and cavernous sinus in a patient with an upper extremity hemodialysis fistula and ipsilateral acute central venous thrombosis. The patient’s symptoms improved after surgical closure of the hemodialysis fistula.     

Nivolumab-induced Vogt-Koyanagi-Harada-like Syndrome and Adrenocortical Insufficiency with Long-term Survival in a Patient with Non-small-cell Lung Cancer

A 58-year-old man was diagnosed with lung adenocarcinoma with a tumor proportion score of 10%. After six cycles of second-line chemotherapy with nivolumab, he achieved a complete response (CR) but developed uveitis and sensorineural hearing disorder, which were consistent with Vogt-Koyanagi-Harada (VKH)-like syndrome. Simultaneously, pituitary adrenocortical insufficiency was identified. Nivolumab discontinuation and systemic corticosteroid administration resolved these immune-related adverse events (irAEs). The patient has maintained a CR without any chemotherapy for approximately two years. We herein report a patient with a long-term progression-free survival despite chemotherapy discontinuation due to irAEs, including VKH-like syndrome, which were appropriately managed.     

Spontaneous Regression of Small Cell Lung Carcinoma and Associated Hemichorea

The spontaneous regression (SR) of cancer is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and this phenomenon is rare in the case of small cell lung carcinoma (SCLC). We herein report an 83-year-old woman who presented with left-sided hemichorea associated with anti-SOX1 (SOX1-Ab) and -CV2/CRMP5 (CV2/CRMP5-Ab) antibodies with SR following a 7-year interval free of disease progression of SCLC. Hemichorea can present with the coexistence of anti-SOX1 and CV2/CRMP5-Ab with SR after a long interval free of SCLC. The immune response associated with these onco-neural antibodies may become independent of the original tumor trigger and remain active for many years.     

心尖球形综合征的诊断及鉴别诊断

心尖球形综合征的发病机制、诊断、处理及预后均不同与急性冠状动脉综合征,但二者的临床特征类似,很容易误诊误治,因此正确诊断及鉴别诊断具有重要的临床意义。谨就二者的临床特征、心电图、心肌酶学、冠状动脉造影、影象学、心功能等改变的异同,诊断及鉴别诊断进行了综述,并对心尖球形综合征的发病机制进行了探讨。